DESCRIPTION: (Applicant's Abstract) Tobacco use is disproportionately high among those with severe psychiatric disorders, such as schizophrenia and affective disorders. The reported prevalence of smoking ranges from 74-90% among schizophrenic patients, to 45-75% among patients with major depression, as compared to 28% in the general population. Not only is tobacco use more prevalent, but psychiatric patients who smoke are also more likely to smoke heavily, to use high tar and nicotine cigarettes, and to have smoked for a longer period of time than smokers from the general population. If the serious health risks associated with smoking are to be prevented in the psychiatric population, it is first necessary to have a greater understanding of why patients smoke so heavily. The aim of this research is to study the involvement of serotonin in regulating psychopathologic symptoms and cigarette smoking among patients with major psychiatric disorders. The prediction is that a serotonin depletion challenge will increase depression and cigarette smoking among depressed patients, while decreasing negative symptoms and cigarette smoking among schizophrenic patients. Results will enhance understanding of the neurochemical and behavioral processes of cigarette smoking and will have implications for designing behavioral and pharmacologic treatments for tobacco dependence in psychiatric patients.